Which JAK Inhibitors Are Clinicians Prescribing for Myelofibrosis?

By Ruben Mesa, MD, Naveen Pemmaraju, MD, Sanam Loghavi, MD, Olatoyosi Odenike, MD - Last Updated: July 2, 2024

A roundtable discussion, moderated by Ruben Mesa, MD, of the Atrium Health Wake Forest Baptist Comprehensive Cancer Center, focused on the latest updates in myeloproliferative neoplasms. Dr. Mesa was joined by Naveen Pemmaraju, MD, of the University of Texas MD Anderson Cancer Center; Sanam Loghavi, MD, of the MD Anderson Cancer Center; and Olatoyosi Odenike, MD, of the University of Chicago Medicine.

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In the next segment of the roundtable series, Drs. Mesa and Pemmaraju share their thoughts on the four Janus kinase (JAK) inhibitors approved by the US Food and Drug Administration for myelofibrosis: ruxolitinib, fedratinib, pacritinib, and momelotinib.

Dr. Mesa: How do you decide which JAK inhibitor to prescribe?

Dr. Pemmaraju: A lot of doctors still feel comfortable with what they know. Ruxolitinib has been around for more than a decade, so that remains the most commonly prescribed medicine regardless of the situation and blood counts. In the clinic, both pacritinib and momelotinib are being used in situations where platelets are less than 50 in the frontline. In the relapse setting, the National Comprehensive Cancer Network guidelines state that it’s potentially okay to prescribe pacritinib even if platelet counts aren’t less than 50 later on. Many patients have anemia, so momelotinib is being prescribed. Most clinicians prescribe ruxolitinib frontline, then the newer agents [in the] second-line. Fedratinib has not been prescribed as much due to gastrointestinal side effects and stigma from the Wernicke’s encephalopathy black box warning.

The other concept is JAK inhibitor withdrawal syndrome, which I’ve only seen with ruxolitinib. It’s uncommon and can happen particularly in patients with higher spleens and higher doses. There, you may want to be cautious about tapering down before switching to another JAK inhibitor. Some are doing an overlap of JAK inhibitors, so a couple of days where they have dual JAK inhibitor. I’m not sure we studied that properly in clinical trials.

Dr. Mesa: The clinical trials don’t address it. However, as we’ve seen in the FREEDOM study, a patient receiving 15 or 20 mg of ruxolitinib twice a day is probably better off being tapered to a lower level before the change. None of the other medications are faster than ruxolitinib. So, you just have to build some of that in.

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